There is a report on the isolation of said compound (1) as the corresponding ammonium or other salt (Japanese Kokai Publication Hei-6-7176) so far, but-there is no knowing of the compound (1) being ever isolated as crystals of simple substance the compound (1). While the compound (1) can be synthesized from a compound (2) represented by the general formula (2);
its isolation has heretofore been made by several alternative methods such as the method which comprises hydrolyzing the side-chain acyl group of compound (2) enzymatically to give a solution thereof (European Patent Publication Number EP0486153A2), the method which comprises alkaline hydrolysis and subsequent extraction with a solvent to give a solution thereof (Japanese Kokai Publication Sho-56-122375), and the method which comprises extracting a culture medium containing compound (1) with a solvent to give an extract solution thereof (Japanese Kokai Publication Hei-6-7176), among others, but what is isolated is invariably a solution.
These prior art methods of obtaining compound (1) presented several problems in commercial application. For example, when the final product is obtained in solution form, it is inevitable that, unless a solvent substitution is carried out, the reaction solvent species which can be used in the next step is restricted to the solvent species used for deacylation or extraction or a mixture solvent containing the same solvent species. Moreover, the product in the form of a solution is inconvenient in handling, e.g. transport and storage, thus having problems in the scope of utility as a universal intermediate. Furthermore, while pharmaceutical intermediates in general are required to be of high quality, the purification technology is self-limited when the substances to be purified are available only in solution form, and although the ion-exchange purification method or the like can be utilized, high-purity products can hardly be obtained by using a multi-purpose equipment at low cost.
Furthermore, although the isolation in the form of an ammonium salt is known according to Japanese Kokai Publication Hei-6-7176, generally the isolation of a salt not only calls for time-consuming solvent substitution with a solvent system which is suited to separation and the presence of a carboxyl group-containing impurity interferes with efficient purification; thus salts of necessity impose a limitation on the solvent species which can be used in the next step, with the result that the method is by no means a commercially recommendable method.